The metabolism of opioid peptides, met5-enkephalin and met5-enkephalin-arg6phe7 (YGGFMRF) was studied both in vitro and in vivo. Both met5-enkephalin and YGGFMRF are readily hydrolyzed by dipeptidyl carboxypeptidase. These two enzyme activities, YGGFMRF hydrolyzing activity and enkephalin inactivating activity (enkephalinase), can be differentially inhibited by specific inhibitors captopril (for YGGFMRF hydrolysis) and thiorphan (for enkephalinase). Using these inhibitors, the possible role of the dipeptidyl carboxypeptidase in metabolism of met5-enkephalin and YGGFMRF were studied in vivo. The thiorphan injected intracerebrally into mice increased the striatal content of met5-enkephalin and also the jump latency from the hot plate. The captopril administration intracerebrally, on the other hand, elevated the striatal content of YGGFMRF in the mice. In the rats, this treatment was found to increase the duration of acupuncture induced analgesia and also the striatal YGGFMRF content by 100%. The results indicate that activity of endogenous opioid system can be activated pharmacologically. The effect of the drug, inhibitor of dipeptidyl carboxypeptidase, on endogenous YGGFMR will be continuously explored in area such as spinal cord, pituitary, lung and heart.